David E. Fleischer

Radiofrequency Ablation in Barrett's Esophagus with Dysplasia

BACKGROUND Barretts esophagus, a condition of intestinal metaplasia of the esophagus, is associated with an increased risk of esophageal adenocarcinoma. We assessed whether endoscopic radiofrequency ablation could eradicate dysplastic Barretts esophagus and decrease the rate of neoplastic progression. METHODS In a multicenter, sham-controlled trial, we randomly assigned 127 patients with dysplastic Barretts esophagus in a 2:1 ratio to receive either radiofrequency ablation (ablation group) or a sham procedure (control group). Randomization was stratified according to the grade of dysplasia and the length of Barretts esophagus. Primary outcomes at 12 months included the complete eradication of dysplasia and intestinal metaplasia. RESULTS In the intention-to-treat analyses, among patients with low-grade dysplasia, complete eradication of dysplasia occurred in 90.5% of those in the ablation group, as compared with 22.7% of those in the control group (P<0.001). Among patients with high-grade dysplasia, complete eradication occurred in 81.0% of those in the ablation group, as compared with 19.0% of those in the control group (P<0.001). Overall, 77.4% of patients in the ablation group had complete eradication of intestinal metaplasia, as compared with 2.3% of those in the control group (P<0.001). Patients in the ablation group had less disease progression (3.6% vs. 16.3%, P=0.03) and fewer cancers (1.2% vs. 9.3%, P=0.045). Patients reported having more chest pain after the ablation procedure than after the sham procedure. In the ablation group, one patient had upper gastrointestinal hemorrhage, and five patients (6.0%) had esophageal stricture. CONCLUSIONS In patients with dysplastic Barretts esophagus, radiofrequency ablation was associated with a high rate of complete eradication of both dysplasia and intestinal metaplasia and a reduced risk of disease progression. (ClinicalTrials.gov number, NCT00282672.)

A Meta-Analysis of the Yield of Capsule Endoscopy Compared to Other Diagnostic Modalities in Patients with Obscure Gastrointestinal Bleeding

OBJECTIVES:Due to its superior ability to examine the entire small bowel mucosa, capsule endoscopy (CE) has broadened the diagnostic evaluation of patients with obscure gastrointestinal bleeding (OGIB). Published studies have revealed a numerically superior performance of CE in determining a source of OGIB compared with other modalities, but due to small sample sizes, the overall magnitude of benefit is unknown. Additionally, the types of lesions more likely to be found by CE versus alternate modalities are also unknown. The aim of this study was to evaluate the yield of small bowel findings with CE in patients with OGIB compared to other modalities using meta-analysis.METHODS:We performed a recursive literature search of prospective studies comparing the yield of CE to other modalities in patients with OGIB. Data on yield and types of lesions identified among various modalities were extracted, pooled, and analyzed. Incremental yield (IY) (yield of CE–yield of comparative modality) and 95% confidence intervals (95% CI) of CE over comparative modalities were calculated.RESULTS:A total of 14 studies (n = 396) compared the yield of CE with push enteroscopy for OGIB. The yield for CE and push enteroscopy was 63% and 28%, respectively (IY = 35%, p < 0.00001, 95% CI = 26–43%) and for clinically significant findings (n = 376) was 56% and 26%, respectively (IY = 30%, p < 0.00001, 95% CI = 21–38%). Three studies (n = 88) compared the yield of CE to small bowel barium radiography. The yield for CE and small bowel barium radiography for any finding was 67% and 8%, respectively (IY = 59%, p < 0.00001, 95% CI = 48–70%) and for clinically significant findings was 42% and 6%, respectively (IY = 36%, p < 0.00001, 95% CI = 25–48%). Number needed to test (NNT) to yield one additional clinically significant finding with CE over either modality was 3 (95% CI = 2–4). One study each compared the yield of significant findings on CE to intraoperative enteroscopy (n = 42, IY = 0%, p = 1.0, 95% CI =−16% to 16%), computed tomography enteroclysis (n = 8, IY = 38%, p = 0.08, 95% CI =−4% to 79%), mesenteric angiogram (n = 17, IY =−6%, p = 0.73, 95% CI =−39% to 28%), and small bowel magnetic resonance imaging (n = 14, IY = 36%, p = 0.007, 95% CI = 10–62%). Ten of the 14 trials comparing CE with push enteroscopy classified the types of lesions found on examination. CE had a 36% yield for vascular lesions versus 20% for push enteroscopy, with an IY of 16% (p < 0.00001, 95% CI = 9–23%). Inflammatory lesions were also found more often in CE (11%) than in push enteroscopy (2%), with an IY of 9% (p = 0.0001, 95% CI = 5–13%). There was no significant difference in the yield of tumors or “other” findings between CE and push enteroscopy.CONCLUSIONS:CE is superior to push enteroscopy and small bowel barium radiography for diagnosing clinically significant small bowel pathology in patients with OGIB. In study populations, the IY of CE over push enteroscopy and small bowel barium radiography for clinically significant findings is ≥30% with an NNT of 3, primarily due to visualization of additional vascular and inflammatory lesions by CE.

A Meta-Analysis of the Yield of Capsule Endoscopy Compared to Other Diagnostic Modalities in Patients with Non-Stricturing Small Bowel Crohn's Disease

OBJECTIVES:Capsule endoscopy (CE) allows for direct evaluation of the small bowel mucosa in patients with Crohns disease (CD). A number of studies have revealed significantly improved yield for CE over other modalities for the diagnosis of CD, but as sample sizes have been small, the true degree of benefit is uncertain. Additionally, it is not clear whether patients with a suspected initial presentation of CD and those with suspected recurrent disease are equally likely to benefit from CE. The aim of this study was to evaluate the yield of CE compared with other modalities in symptomatic patients with suspected or established CD using meta-analysis.METHODS:We performed a recursive literature search of prospective studies comparing the yield of CE to other modalities in patients with suspected or established CD. Data on yield among various modalities were extracted, pooled, and analyzed. Incremental yield (IY) (yield of CE − yield of comparative modality) and 95% confidence intervals (95% CI) of CE over comparative modalities were calculated. Subanalyses of patients with a suspected initial presentation of CD and those with suspected recurrent disease were also performed.RESULTS:Nine studies (n = 250) compared the yield of CE with small bowel barium radiography for the diagnosis of CD. The yield for CE versus barium radiography for all patients was 63% and 23%, respectively (IY = 40%, p < 0.001, 95% CI = 28–51%). Four trials compared the yield of CE to colonoscopy with ileoscopy (n = 114). The yield for CE versus ileoscopy for all patients was 61% and 46%, respectively (IY = 15%, p= 0.02, 95% CI = 2–27%). Three studies compared the yield of CE to computed tomography (CT) enterography/CT enteroclysis (n = 93). The yield for CE versus CT for all patients was 69% and 30%, respectively (IY = 38%, p= 0.001, 95% CI = 15–60%). Two trials compared CE to push enteroscopy (IY = 38%, p < 0.001, 95% CI = 26–50%) and one trial compared CE to small bowel magnetic resonance imaging (MRI) (IY = 22%, p= 0.16, 95% CI =−9% to 53%). Subanalysis of patients with a suspected initial presentation of CD showed no statistically significant difference between the yield of CE and barium radiography (p= 0.09), colonoscopy with ileoscopy (p= 0.48), CT enterography (p= 0.07), or push enteroscopy (p= 0.51). Subanalysis of patients with established CD with suspected small bowel recurrence revealed a statistically significant difference in yield in favor of CE compared with all other modalities (barium radiography (p < 0.001), colonoscopy with ileoscopy (p= 0.002), CT enterography (p < 0.001), and push enteroscopy (p < 0.001)).CONCLUSIONS:In study populations, CE is superior to all other modalities for diagnosing non-stricturing small bowel CD, with a number needed to test (NNT) of 3 to yield one additional diagnosis of CD over small bowel barium radiography and NNT = 7 over colonoscopy with ileoscopy. These results are due to a highly significant IY with CE over all other modalities in patients with established non-stricturing CD being evaluated for a small bowel recurrence. While there was no significant difference seen between CE and alternate modalities for diagnosing small bowel CD in patients with a suspected initial presentation of CD, the trend toward significance for a number of modalities suggests the possibility of a type II error. Larger studies are needed to better establish the role of CE for diagnosing small bowel CD in patients with a suspected initial presentation of CD.

Durability of Radiofrequency Ablation in Barrett's Esophagus With Dysplasia

BACKGROUND & AIMS Radiofrequency ablation (RFA) can eradicate dysplasia and intestinal metaplasia in patients with dysplastic Barretts esophagus (BE), and reduce rates of esophageal adenocarcinoma. We assessed long-term rates of eradication, durability of neosquamous epithelium, disease progression, and safety of RFA in patients with dysplastic BE. METHODS We performed a randomized trial of 127 subjects with dysplastic BE; after cross-over subjects were included, 119 received RFA. Subjects were followed for a mean time of 3.05 years; the study was extended to 5 years for patients with eradication of intestinal metaplasia at 2 years. Outcomes included eradication of dysplasia or intestinal metaplasia after 2 and 3 years, durability of response, disease progression, and adverse events. RESULTS After 2 years, 101 of 106 patients had complete eradication of all dysplasia (95%) and 99 of 106 had eradication of intestinal metaplasia (93%). After 2 years, among subjects with initial low-grade dysplasia, all dysplasia was eradicated in 51 of 52 (98%) and intestinal metaplasia was eradicated in 51 of 52 (98%); among subjects with initial high-grade dysplasia, all dysplasia was eradicated in 50 of 54 (93%) and intestinal metaplasia was eradicated in 48 of 54 (89%). After 3 years, dysplasia was eradicated in 55 of 56 of subjects (98%) and intestinal metaplasia was eradicated in 51 of 56 (91%). Kaplan-Meier analysis showed that dysplasia remained eradicated in >85% of patients and intestinal metaplasia in >75%, without maintenance RFA. Serious adverse events occurred in 4 of 119 subjects (3.4%); the rate of stricture was 7.6%. The rate of esophageal adenocarcinoma was 1 per 181 patient-years (0.55%/patient-years); there was no cancer-related morbidity or mortality. The annual rate of any neoplastic progression was 1 per 73 patient-years (1.37%/patient-years). CONCLUSIONS In subjects with dysplastic BE, RFA therapy has an acceptable safety profile, is durable, and is associated with a low rate of disease progression, for up to 3 years.

Double-Balloon Enteroscopy and Capsule Endoscopy Have Comparable Diagnostic Yield in Small-Bowel Disease: A Meta-Analysis

BACKGROUND & AIMS The aim of this study was to compare the diagnostic yield of capsule endoscopy (CE) with double-balloon enteroscopy (DBE) in small-bowel (SB) disease using meta-analysis. METHODS We performed a search of studies comparing CE with DBE in SB disease. Data on diagnostic yield of CE and DBE were extracted, pooled, and analyzed. The weighted incremental yield (IY(W)) (yield of CE--yield of DBE) of CE over DBE and 95% confidence intervals (95% CIs) for pooled data were calculated using a fixed-effect model (FEM) for analyses without, and a random-effect model (REM) for analyses with, significant heterogeneity. RESULTS Eleven studies compared CE and DBE; the pooled overall yield for CE and DBE was 60% (n = 397) and 57% (n = 360), respectively (IY(W), 3%; 95% CI, -4% to 10%; P = .42; FEM). Ten studies reported vascular findings; the pooled yield for CE and DBE was 24% (n = 371) and 24% (n = 364), respectively (IY(W), 0%; 95% CI, -5% to 6%; P = .88; REM). Nine studies reported inflammatory findings; the pooled yield for CE and DBE was 18% (n = 343) and 16% (n = 336), respectively (IY(W), 0%; 95% CI, -5% to 6%; P = .89; FEM). Nine studies reported polyps/tumors; the pooled yield for CE and DBE was 11% (n = 343) and 11% (n = 336), respectively (IY(W), -1%; 95% CI, -5% to 4%; P = .76; FEM). CONCLUSIONS CE and DBE have comparable diagnostic yield in SB disease, including obscure gastrointestinal bleeding. CE should be the initial diagnostic test because of its noninvasive quality, tolerance, ability to view the entire SB, and for determining the initial route of DBE. Because of its therapeutic capabilities, DBE may be indicated in patients with a positive finding on CE requiring a biopsy or therapeutic intervention, if suspicion for a SB lesion is high despite a negative CE, and in patients with active bleeding.

Capsule endoscopy has a significantly higher diagnostic yield in patients with suspected and established small-bowel Crohn's disease: a meta-analysis

OBJECTIVES:Capsule endoscopy (CE) has demonstrated superior performance compared with other modalities in its ability to detect early small-bowel (SB) Crohns disease (CD), especially when ileoscopy is negative or unsuccessful. The aim of this study was to evaluate the diagnostic yield of CE compared with other modalities in patients with suspected and established CD using a meta-analysis.METHODS:A thorough literature search for prospective studies comparing the diagnostic yield of CE with other modalities in patients with CD was undertaken. Other modalities included push enteroscopy (PE), colonoscopy with ileoscopy (C+IL), SB radiography (SBR), computed tomography enterography (CTE), and magnetic resonance enterography (MRE). Data on diagnostic yield among various modalities were extracted, pooled, and analyzed. Data on patients with suspected and established CD were analyzed separately. Weighted incremental yield (IYW) (diagnostic yield of CE−diagnostic yield of comparative modality) and 95% confidence intervals (CIs) of CE over comparative modalities were calculated.RESULTS:A total of 12 trials (n=428) compared the yield of CE with SBR in patients with CD. Eight trials (n=236) compared CE with C+IL, four trials (n=119) compared CE with CTE, two trials (n=102) compared CE with PE, and four trials (n=123) compared CE with MRE. For the suspected CD subgroup, several comparisons met statistical significance. Yields in this subgroup were CE vs. SBR: 52 vs. 16% (IYw=32%, P<0.0001, 95% CI=16–48%), CE vs. CTE: 68 vs. 21% (IYw=47%, P<0.00001, 95% CI=31–63%), and CE vs. C+IL: 47 vs. 25% (IYw=22%, P=0.009, 95% CI=5–39%). Statistically significant yields for CE vs. an alternate diagnostic modality in established CD patients were seen in CE vs. PE: 66 vs. 9% (IYw=57%, P<0.00001, 95% CI=43–71%), CE vs. SBR: 71 vs. 36% (IYw=38%, P<0.00001, 95% CI=22–54%), and in CE vs. CTE: 71 vs. 39% (IYw=32%, P=<0.0001, 95% CI=16–47%).CONCLUSIONS:Our meta-analysis demonstrates that CE is superior to SBR, CTE, and C+IL in the evaluation of suspected CD patients. CE is also a more effective diagnostic tool in established CD patients compared with SBR, CTE, and PE.

A single-center experience of 260 consecutive patients undergoing capsule endoscopy for obscure gastrointestinal bleeding.

OBJECTIVES:Capsule endoscopy (CE) has revolutionized the evaluation of obscure gastrointestinal bleeding (OGIB) but published literature is limited to small series with heterogeneous indications. The aim of this study was to determine the findings and the diagnostic yield of CE in a large series of patients with overt and occult OGIB.METHODS:Data on 260 patients who underwent CE for overt (N = 126) or occult (N = 134) OGIB were obtained by retrospective chart review and review of an internal database of CE patients and findings.RESULTS:Visualization of the entire small bowel was achieved in 74%. The majority of exams (66%) were rated as having a good or excellent prep. Clinically significant positive findings occurred in 53%. The yield of CE in the obscure-overt group was greater than in the obscure-occult group (60% vs 46%, P = 0.03). Small bowel angioectasias were the most common finding, comprising over 60% of clinically significant lesions. The mean follow-up was 9.6 months, and there were significant reductions in hospitalizations, additional tests/procedures, and units of blood transfused after CE. Both before and after CE, patients in the overt group had more significant GI bleeding than patients in the occult group. Complications occurred in five (1.9%) cases: nonnatural excretion (four) and CE impaction at cricopharyngeus (one).CONCLUSIONS:The yield of clinically important findings on CE in patients with OGIB is 53% and is greater in patients with obscure-overt than obscure-occult GI bleeding. Angioectasias account for the majority of significant lesions in both groups. Compared with pre-CE, patients had clinical improvement post-CE in medical interventions for OGIB. Complications of CE occur in less than 2% of cases.

Circumferential ablation of Barrett's esophagus that contains high-grade dysplasia: a U.S. multicenter registry

BACKGROUND The management strategies for Barretts esophagus (BE) that contains high-grade dysplasia (HGD) include intensive endoscopic surveillance, photodynamic therapy, thermal ablation, EMR, and esophagectomy. OBJECTIVE To assess the safety and effectiveness of endoscopic circumferential balloon-based ablation by using radiofrequency energy for treating BE HGD. DESIGN Multicenter U.S. registry. SETTING Sixteen academic and community centers; treatment period from September 2004 to March 2007. PATIENTS Patients with histologic evidence of intestinal metaplasia (IM) that contained HGD confirmed by at least 2 expert pathologists. A prior EMR was permitted, provided that residual HGD remained in the BE region for ablation. INTERVENTION Endoscopic circumferential ablation with follow-up esophageal biopsies to assess the histologic response to treatment. OUTCOMES Histologic complete response (CR) end points: (1) all biopsy specimen fragments obtained at the last biopsy session were negative for HGD (CR-HGD), (2) all biopsy specimens were negative for any dysplasia (CR-D), and (3) all biopsy specimens were negative for IM (CR-IM). RESULTS A total of 142 patients (median age 66 years, interquartile range [IQR] 59-75 years) who had BE HGD (median length 6 cm, IQR 3-8 cm) underwent circumferential ablation (median 1 session, IQR 1-2). No serious adverse events were reported. There was 1 asymptomatic stricture and no buried glands. Ninety-two patients had at least 1 follow-up biopsy session (median follow-up 12 months, IQR 8-15 months). A CR-HGD was achieved in 90.2% of patients, CR-D in 80.4%, and CR-IM in 54.3%. LIMITATIONS A nonrandomized study design, without a control arm, a lack of centralized pathology review, ablation and biopsy technique not standardized, and a relatively short-term follow-up. CONCLUSIONS Endoscopic circumferential ablation is a promising modality for the treatment of BE that contains HGD. In this multicenter registry, the intervention safely achieved a CR for HGD in 90.2% of patients at a median of 12 months of follow-up.

Endoscopic radiofrequency ablation for Barrett's esophagus: 5-year outcomes from a prospective multicenter trial.

BACKGROUND AND STUDY AIMS The AIM-II Trial included patients with nondysplastic Barretts esophagus (NDBE) treated with radiofrequency ablation (RFA). Complete eradication of NDBE (complete response-intestinal metaplasia [CR-IM]) was achieved in 98.4 % of patients at 2.5 years. We report the proportion of patients demonstrating CR-IM at 5-year follow-up. PATIENTS AND METHODS Prospective, multicenter US trial (NCT00489268). After endoscopic RFA of NDBE up to 6 cm, patients with CR-IM at 2.5 years were eligible for longer-term follow-up. At 5 years, we obtained four-quadrant biopsies from every 1 cm of the original extent of Barretts esophagus. All specimens were reviewed by one expert gastrointestinal pathologist, followed by focal RFA and repeat biopsy if NDBE was identified. Primary outcomes were (i) proportion of patients demonstrating CR-IM at 5-year biopsy, and (ii) proportion of patients demonstrating CR-IM at 5-year biopsy or after the single-session focal RFA. RESULTS Of 60 eligible patients, 50 consented to participate. Of 1473 esophageal specimens obtained at 5 years 85 % contained lamina propria or deeper tissue (per patient, mean 30 , standard deviation [SD] 13). CR-IM was demonstrated in 92 % (46 / 50) of patients, while 8 % (4 / 50) had focal NDBE; focal RFA converted all these to CR-IM. There were no buried glands, dysplasia, strictures, or serious adverse events. Kaplan-Meier CR-IM survival analysis showed probability of maintaining CR-IM for at least 4 years after first durable CR-IM was 0.91 (95 % confidence interval [CI] 0.77 - 0.97) and mean duration of CR-IM was 4.22 years (standard error [SE] 0.12). CONCLUSIONS In patients with NDBE treated with RFA, CR-IM was demonstrated in the majority of patients (92 %) at 5-year follow-up, biopsy depth was adequate to detect recurrence, and all failures (4 / 4, 100 %) were converted to CR-IM with single-session focal RFA.

Endoscopic ablation of Barrett's esophagus: a multicenter study with 2.5-year follow-up

BACKGROUND For patients with Barretts esophagus (BE), life-long surveillance endoscopy is recommended because of an elevated risk for developing dysplasia and esophageal adenocarcinoma. Various endoscopic therapies have been used to eradicate BE. Recently circumferential radiofrequency ablation has been used with encouraging short-term results. OBJECTIVE To provide longer follow-up and to assess the long-term safety and efficacy of step-wise circumferential ablation with the addition of focal ablation for BE. DESIGN Prospective, multicenter clinical trial (NCT00489268). SETTING Eight U.S. centers, between May 2004 and February 2007. PATIENTS Seventy subjects with 2 to 6 cm of BE and histologic evidence of intestinal metaplasia (IM). INTERVENTIONS Circumferential ablation was performed at baseline and repeated at 4 months if there was residual IM. Follow-up biopsy specimens were obtained at 1, 3, 6, 12, and 30 months. Specimens were reviewed by a central pathology board. Focal ablation was performed after the 12-month follow-up for histological evidence of IM at the 12-month biopsy (absolute indication) or endoscopic appearance suggestive of columnar-lined esophagus (relative indication). Subjects received esomeprazole for control of esophageal reflux. MAIN OUTCOME MEASUREMENTS Complete absence of IM per patient from biopsy specimens obtained at 12 and 30 months, defined as complete remission-IM (CR-IM). RESULTS At 12 months, CR-IM was achieved in 48 of 69 available patients (70% per protocol [PP], 69% intention to treat [ITT]). At 30 months after additional focal ablative therapy, CR-IM was achieved in 60 of 61 available patients (98% PP, 97% ITT). There were no strictures or buried glandular mucosa detected by the standardized biopsy protocol at 12 or 30 months, and there were no serious adverse events. LIMITATIONS This was an uncontrolled clinical trial with 2.5-year follow-up. CONCLUSION Stepwise circumferential and focal ablation resulted in complete eradication of IM in 98% of patients at 2.5-year follow-up.